Elucidating the Role of Lasp-2 in Cell Adhesion and Migration

Abstract

In order for cells to migrate, communicate, and facilitate attachment to the surrounding extraceullar matrix, they must form intricate protein complexes called focal adhesions. The number of identified focal adhesion components continues to grow and the field is an area of active study.Lasp-2 is a member of the nebulin family of actin-binding proteins that has been identified as a member of focal adhesion complexes. To gain further insights into the functional role of lasp-2, we identified two additional binding partners of lasp-2, the integral focal adhesion proteins, vinculin and paxillin. Interestingly, the interaction of lasp-2 with its binding partners vinculin and paxillin was significantly reduced in presence of lasp-1, another nebulin family member. The presence of lasp-2 appears to enhance the interaction of vinculin and paxillin with each other, however, as with the interaction of lasp-2 with vinculin or paxillin, this effect is greatly diminished in the presence of excess lasp-1 suggesting the interplay between lasp-2 and lasp-2 could be an adhesion regulatory mechanism. Lasp-2's potential role in metastasis was revealed as overexpression of lasp-2 in SW620 cells, a highly metastatic cancer cell line, increased cell migration, but impeded cell invasion.Lasp-2 transcript and protein is readily detected in neural tissues. Preliminary experiments involving the knockdown of lasp-2- in frog embryos revealed gross morphological abnormalities in the head region as well as the inability to move normally. Neural crest derived melanocytes also failed to migrate normally.Taken together, these data suggest that lasp-2 has an important role in coordinating and regulating the composition and dynamics of focal adhesions.